Effect Mechanism of Electrocardiogram-Based Intravenous Single-Walled Carbon Nanotubes on Cardiac Function

Abstract

This research was aimed to adopt electrocardiogram (ECG) and other techniques to explore the effects and mechanisms of single-walled carbon nanotubes (SWCNTs) and their carboxylation modification (C-SWCNTs) on cardiac function in rats. The SWCNTs were oxidized to C-SWCNTs by concentrated sulfuric acid and concentrated nitric acid. The morphology, surface charge, surface group, and water dispersibility of the samples were characterized. Subsequently, 40 SD rats in a 1:1:1:1 ratio were assigned into sham (intravenous injection of 5% glucose), SWCNT (intravenous injection of 2 mg/mL SWCNT glucose dispersion), C-SWCNT (intravenous injection of 2 mg/mL C-SWCNT glucose dispersion), and C-SWCNT+YM groups (treatment in C-SWCNT group was supplemented with an additional 1 mg/mL store-operated calcium entry (SOCE) blocker YM-58483/BTP2). The tail arterial pressure of rats in each group was detected. Left heart function and hemodynamics were detected by cardiac color ultrasonography. Heart parameters were detected by ECG lead II, and the pathological morphology of the heart was detected by hematoxylin-eosin staining. The levels of proteins related to the cardiac calcium signaling were detected by western blot. The results showed that the particle size distributions of SWCNTs and C-SWCNTs were uniform, and C-SWCNTs had better water dispersibility and a negatively charged surface. The results of caudal arterial pressure showed that SBP, DBP, and MBP of the caudal arteries in the SWCNT and C-SWCNT groups were markedly superior to those in sham group (P < 0.05). Cardiac function results showed drastic decreases in LVDd, EF, EDV, SV, and CO and great increases in LVDs, AV-BVmax, and PV-BVmax in the SWCNT and C-SWCNT groups relative to sham group (P < 0.05). The ECG results showed that relative to those in sham group, the amplitudes of the P wave and ST segment in the SWCNT and C-SWCNT groups were increased, the QRS and RR intervals were greatly prolonged, and the amplitude of the R wave was greatly decreased (P < 0.05). Western blot results showed that the SWCNT and C-SWCNT groups had drastically increased protein levels of ORAI-1 and STIM-1 in the heart versus sham group (P < 0.05). The changes in various cardiac parameters in C-SWCNT group were more prominent, and the cardiac pathological score increased markedly versus that in SWCNT group. The protein levels of ORAI-1 and STIM-1 increased notably (P < 0.05). The changes in various cardiac parameters in C-SWCNT+YM group were notably enhanced versus those in the SWCNT and C-SWCNT groups, the cardiac pathological score was obviously reduced, and the protein levels of ORAI-1 and STIM-1 were substantially decreased (P < 0.05). SWCNTs and C-SWCNTs both had cardiotoxic effects in rats, and C-SWCNTs had more obvious toxic effects. Nevertheless, the SOCE inhibitor YM-58483/BTP2 was able to enhance C-SWCNT-induced cardiac dysfunction by inhibiting the expression of calcium signaling-related proteins and affecting the changes in ECG parameters.